Age-associated T cell immunity decreases circulating endothelial progenitor cells
Fang Zhang1, Qiuchen Zhao2, Shuzhen Guo1
1Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, United States.
Stem Cells (Dayton, Ohio)
|October 23, 2025
Summary
Aging reduces circulating endothelial progenitor cells (EPCs) by increasing inhibitory T cells and FABP4, impairing vascular health. Targeting FABP4 or using mitochondria therapy may reverse this decline and combat vascular aging.
Area of Science:
- Gerontology
- Immunology
- Vascular Biology
Background:
- Circulating endothelial progenitor cells (EPCs) decline with vascular aging.
- Mechanisms driving this EPC reduction are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms behind age-related EPC decline.
- To investigate the role of FABP4 and T cells in vascular aging.
Main Methods:
- SomaScan proteomics and western blot analysis identified FABP4.
- In vitro and in vivo experiments using FABP4 inhibitors (BMS309403), T cell depletion, and mitochondria therapy in aged mice.
Main Results:
- Aging elevates plasma and bone marrow FABP4.
- FABP4 promotes inhibitory T cells and reduces CXCR4 expression on EPCs.
- Blocking FABP4 or depleting T cells restored EPC CXCR4 expression.
- Mitochondria therapy decreased FABP4, reduced inhibitory T cells, and increased circulating EPCs in aged mice.
Conclusions:
- Age-associated T cell immunity contributes to EPC dysregulation.
- FABP4 is a key mediator in age-related EPC decline.
- FABP4 represents a potential therapeutic target for vascular aging.
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